How do I manage hyperglycemia/post-transplant diabetes mellitus after allogeneic HSCT.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients frequently develop glucose intolerance and post-transplant diabetes mellitus (PTDM). The clinical importance of PTDM and its detrimental impact on HSCT outcomes are under-recognized. After allo-HSCT, various mechanisms can contribute to the development of PTDM. Here we review information about hyperglycemia and PTDM after allo-HSCT as well as PTDM after solid organ transplantation and describe ways to manage hyperglycemia/PTDM after allogeneic HSCT. Taking into consideration a lack of well-established evidence in the field of allo-HSCT, more studies should be conducted in the future, which will require closer multidisciplinary collaboration between hematologists, endocrinologists and nutritionists.

Six-month freedom from treatment failure is an important end point for acute GVHD clinical trials.

We studied the American Society for Blood and Marrow Transplantation (ASBMT) 6-month (m) freedom from treatment failure (FFTF) as a predictor of survival for patients with acute GVHD (aGVHD) requiring treatment. Adult patients undergoing allogeneic hematopoietic cell transplant (HCT) from February 2007 to March 2009 who were enrolled in a prospective biomarker clinical trial and developed aGVHD requiring systemic corticosteroids by day +100 were included (N=44). Six-month FFTF was defined as per the ASBMT guidelines (absence of death, malignancy relapse/progression or systemic immunosuppression change within 6 months of starting steroids and before chronic GVHD development). aGVHD was treated with systemic corticosteroids in 44 patients. Day 28 response after steroid initiation (complete response+very good partial response+partial response) occurred in 38 (87%) patients, but only 28 (64%) HCT recipients met the 6-m FFTF end point. Day 28 response predicted 6-m FFTF. Achieving 6-m FFTF was associated with improved 2-year (y) OS (81% vs 48%; P=0.03) and decreased 2-y non-relapse mortality (8% vs 49%; P=0.01). In multivariate analysis, 6-m FFTF continued to predict improved OS (hazard ratio, 0.27; P=0.03). The 6-m FFTF end point measures fixed outcomes, predicts long-term therapeutic success and could be less prone to measurement error than aGVHD clinical response at day 28.

Allo-SCT for high-risk AML-CR1 in the molecular era: impact of FLT3/ITD outweighs the conventional markers.

Seventy-nine patients with AML in CR1 received allo-SCT between May 2006 and May 2011, and the prognostic impact of FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD) mutation was evaluated in the context of other clinical prognostic factors. Patients with FLT3/ITD + AML had significantly inferior DFS (2-year DFS: 19% vs 64%, P = 0.0027), increased risk of relapse (1-year: 59% vs 19%, P = 0.01), and a trend towards decreased OS (P = 0.08) compared with patients without FLT3/ITD. Multivariate analysis confirmed FLT3/ITD + independently predicted a shorter DFS (HR, 3.0; 95% CI), 1.4-6.5; P = 0.01) and increased risk of relapse (HR, 4.9; 95% CI, 2.0-12.3, P = 0.01). Time to relapse in patients with FLT3/ITD + was short with 100-day cumulative risk of 45% (95% CI, 33-57). Our data suggest that the poor prognostic implication of FLT3/ITD positivity remains even after early allo-SCT in patients with FLT3/ITD + AML, and patients remain at high risk of early relapse. FLT3/ITD positivity also outweighs other conventional prognostic markers in predicting relapse.

Prevalence and risk factors associated with development of ocular GVHD defined by NIH consensus criteria.

We studied 172 patients for development of ocular graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT) from 2002 to 2009. Ocular GVHD was diagnosed in 60 patients (38%), with 27 (16%) being diagnosed at days 100 and 33 (23%) beyond day 100 for a 2-year cumulative incidence of 35% (95% confidence interval (CI), 28-43). The positive and negative predictive values of a Schirmer I test score (using 5 mm as a cutoff) in predicting ocular GVHD (day 100) were 41 and 82%, respectively. In patients with ocular GVHD beyond day 100, extraocular manifestations of GVHD preceded the development of ocular GVHD in most patients (27 of 33, 81%). Prior acute skin GVHD (odds ratio 2.57, 95% CI 1.17-5.64, P=0.019) and male recipients of female donors (odds ratio 2.57, 95% CI 1.09-6.06, P=0.03) were independent risk factors for ocular GVHD. We recommend comprehensive ocular evaluation rather than a screening Schirmer's test to establish the diagnosis of ocular GVHD. Early diagnosis and preventive strategies in high-risk populations need to be studied in clinical trials to prevent devastating impact on quality of life in patients with prolonged ocular GVHD.

Regulatory T cell expression of CLA or α(4)ß(7) and skin or gut acute GVHD outcomes.

Regulatory T cells (Tregs) are a suppressive subset of CD4(+) T lymphocytes implicated in the prevention of acute GVHD (aGVHD) after allo-SCT (ASCT). To determine whether increased frequency of Tregs with a skin-homing (cutaneous lymphocyte Ag, CLA(+)) or a gut-homing (α(4)ß(7)(+)) phenotype is associated with reduced risk of skin or gut aGVHD, respectively, we quantified circulating CLA(+) or α(4)ß(7)(+) on Tregs at the time of neutrophil engraftment in 43 patients undergoing ASCT. Increased CLA(+) Tregs at engraftment was associated with the prevention of skin aGVHD (2.6 vs 1.7%; P=0.038 (no skin aGVHD vs skin aGVHD)), and increased frequencies of CLA(+) and α(4)ß(7)(+) Tregs were negatively correlated with severity of skin aGVHD (odds ratio (OR), 0.67; 95% confidence interval (CI), 0.46-0.98; P=0.041) or gut aGVHD (OR, 0.93; 95% CI, 0.88-0.99; P=0.031), respectively. This initial report suggests that Treg tissue-homing subsets help to regulate organ-specific risk and severity of aGVHD after human ASCT. These results need to be validated in a larger, multicenter cohort.

Extracorporeal photopheresis in patients with refractory bronchiolitis obliterans developing after allo-SCT.

Extracorporeal photopheresis (ECP) has been shown to be a promising treatment for chronic graft-versus-host disease; however, only a few case reports are available that examine the effectiveness of ECP for bronchiolitis obliterans (BO) after allo-SCT. Because of the poor response to traditional therapies, ECP has been explored as a possible therapeutic option for severe BO after allo-SCT. Nine patients received ECP between July 2008 and August 2009 after a median follow-up of 23 months (range 9-93 months) post transplant. The primary indication for ECP was the development of BO in patients who had failed prior multidrug regimens. The median number of drugs used for BO management before ECP was 5 (range 2-7); this included immunosuppressive therapy. Six of nine (67%) patients responded to ECP after a median of 25 days (range 20-958 days). No ECP-related complications occurred. ECP seemed to stabilize rapidly declining pulmonary function tests in about two-thirds of patients with severe and heavily pretreated BO that developed after allo-SCT. This finding supports the need for a larger prospective study to confirm the impact of ECP on BO, and to consider earlier intervention with ECP to improve the outcome of BO after allo-SCT.